Mild Cognitive Impairment Dementia Research Articles

High late‐life physical activities and reduced progression from MCI to Alzheimer’s dementia

AbstractBackgroundPhysical activity (PA) has been reported to reduce the risk of Alzheimer`s disease (AD) dementia and related cognitive decline. We aimed to investigate the influence of PA on the progression from cognitively normal (CN) status to mild cognitive impairment (MCI) or from MCI to AD dementia in non‐demented older adults.MethodThis study included 194 non‐demented (148 CN and 46 MCI) participants from the Korean Brain Aging Study for Early diagnosis and prediction of Alzheimer’s disease (KBASE), who completed both baseline and 2‐year follow‐up clinical evaluation. At baseline, the participants underwent comprehensive clinical and neuropsychological assessment, multimodal brain imaging including [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] fluorodeoxyglucose PET and MRI, and current PA measured using the Lifetime Total Physical Activity Questionnaire.ResultAfter 2 years, five CN and 22 MCI participants progressed to MCI and AD dementia, respectively. Logistic regression analyses showed that high current PA (above the median value) reduced the risk of the progression from MCI to AD dementia even after controlling age, sex, education, apolipoprotein E e4 positivity, baseline brain amyloid deposition, AD‐signature region glucose metabolism, and AD‐signature region cortical thickness (Bonferroni corrected p‐value = 0.028). In contrast, PA had no effect on the progression from CN to MCI.ConclusionThe findings suggest that a physically active lifestyle in late‐life reduces the risk of conversion to AD dementia in MCI independently of AD‐related brain pathologies.

Controlling Gut Microbiota by Twendee X® May Contribute to Dementia Prevention.

The human gut microbiota (GM) is a complex and dynamic ecosystem that hosts trillions of commensal and potentially pathogenic microorganisms. It is crucial in protecting humans from pathogens and in maintaining immune and metabolic homeostasis. Numerous studies have demonstrated that GM has a significant impact on health and disease, including Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder characterized by impaired short-term memory and cognitive deficits. Patients with AD have been reported to exhibit abnormalities in GM density and species composition. Oxidative stress (OS) has been implicated in the onset and progression of AD; however, the relationship between OS and gut microbiota in AD onset and progression is not clear. Twendee X® (TwX), an oral supplement consisting of eight active ingredients, has been shown to prevent dementia in mild cognitive impairment (MCI) in humans and substantially improve cognitive impairment in mouse models of AD. This positive effect is achieved through the potency of the combined antioxidants that regulate OS; therefore, similar results cannot be achieved by a single antioxidant ingredient. To examine the impact of long-term OS elevation, as seen in AD on the body and GM, we examined GM alterations during the initial OS elevation using a two-week OS loading rat model, and examined the effects of TwX on OS and GM. Furthermore, using a questionnaire survey and fecal samples, we analyzed the impact of TwX on healthy individuals' gut bacteria and the associated effect on their quality of life (QOL). TwX was found to increase the number of bacteria species and their diversity in GM, as well as butyrate-producing bacteria, which tend to be reduced in AD patients. Additionally, TwX improved defecation condition and QOL. The gut bacteria function as part of the homeostatic function during OS elevation, and the prophylactic administration of TwX strengthened this function. The results suggest that the preventative effect of TwX on dementia may involve the GM, in addition to the other previously demonstrated effects.

Associations between neuropsychiatric symptoms of affective and vegetative domains and brain morphology in aging people with mild cognitive impairment and Alzheimer's disease.

Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and even more in Alzheimer's disease (AD). The symptom-based cluster including nighttime disturbances, depression, appetite changes, anxiety, and apathy (affective and vegetative symptoms) was associated with an increased risk of dementia in MCI and has common neuroanatomical associations. Our objective was to investigate the differences in brain morphology associations with affective and vegetative symptoms between three groups: cognitively normal older adults (CN), MCI and AD. Alzheimer's Disease Neuroimaging Initiative data of 223 CN, 367 MCI and 175 AD, including cortical volumes, surface areas and thicknesses and severity scores of the five NPS were analyzed. A whole-brain vertex-wise general linear model was performed to test for intergroup differences (CN-MCI, CN-AD, AD-MCI) in brain morphology associations with five NPS. Multiple regressions were conducted to investigate cortical change as a function of NPS severity in the AD-MCI contrast. We found (1) signature differences in nighttime disturbances associations with prefrontal regions in AD-MCI, (2) signature differences in NPS associations with temporal regions in AD-MCI for depression and in CN-AD for anxiety, (3) decreased temporal metrics in MCI as nighttime disturbances and depression severity increased, (4) decreased pars triangularis metrics in AD as nighttime disturbances and apathy severity increased. Each NPS seems to have a signature on brain morphology. Affective and vegetative NPS were primarily associated with prefrontal and temporal regions. These signatures open the possibility of potential future assessments of links between brain morphology and NPS on an individual level.

Risk prediction of Alzheimer’s dementia in mild cognitive impairment – Impact of AD biomarker disclosure on quality of life, mental health and risk knowledge: The PreDADQoL study

AbstractBackgroundExpanded technologies in early AD detection have led to an increasing number of individuals with mild cognitive impairment (MCI) asking for biomarker‐based risk prediction of Alzheimer’s dementia. However, standardized approaches for counseling and disclosure of individuals with MCI are lacking in clinical practice. First studies on cognitively healthy individuals and MCI patients have reported no major impact on psychological wellbeing after AD biomarker disclosure, but data on quality of life, health behavior changes and risk knowledge of individuals with MCI before and after AD biomarker disclosure is sparse.MethodThe transnational (Germany and Spain) project PreDADQoL recruited a total of 76 MCI patients and caregivers. Dyads received a standardized counseling on predictive biomarker‐based diagnosis of AD. MCI patients consenting to cerebrospinal fluid (CSF)‐biomarker testing received a standardized disclosure of their biomarker status and consecutive dementia risk. Following a mixed‐methods approach the empirical part of the project conducted follow‐up visits over 3 months to assess the effects of predictive AD diagnosis on various outcomes.ResultCounseling on biomarker‐based AD detection and disclosure of dementia risk has no major impact on mental health and quality of life on MCI patients and their caregivers on short term follow‐up. Although the counseling included recommendations on lifestyle modification, individuals with MCI and caregivers reported a significantly less beneficial lifestyle 3 months after risk disclosure as compared to baseline. Despite adequate numeracy skills, the dementia risk perception in individuals with MCI did not correlate with the communicated risk, whereas caregivers’ risk perception correlated significantly with the communicated risk.ConclusionOur findings confirm that predictive AD diagnosis causes no major harm with regard to mental health and quality of life. However, despite the psychoeducational approach during the counseling and disclosure sessions with facilitating supplies, such as visual aids and take‐home material, the anticipated fostering effects on health behavior and risk knowledge remain modest. Our study contributes to the extended understanding of individuals with MCI and their caregivers when facing early AD detection. The PreDADQoL study will synergize empirical data with ethical and legal considerations for a guidance of good clinical practice in the field of predictive AD diagnosis.

Functional mobility decline and incident mild cognitive impairment and early dementia in community-dwelling older adults: the Singapore Longitudinal Ageing Study.

Motor and gait disturbances are evident in early Alzheimer and non-Alzheimer dementias and may predict the likelihood of mild cognitive impairment (MCI) or progression to dementia. We investigated the Timed-Up-and-Go (TUG) measure of functional mobility in predicting cognitive decline and incident MCI or early dementia (MCI-dementia). Prospective cohort study with 4.5years follow-up. Population based. 2,544 community-dwelling older adults aged 55+ years. Participants with baseline data on TUG, fast gait speed (GS), knee extension strength (KES) and performance-oriented mobility assessment (POMA) gait and balance were followed up for cognitive decline (Mini-Mental State Exam; MMSE drop of ≥2, among 1,336 dementia-free participants) and incident MCI-dementia (among 1,208 cognitively normal participants). Odds ratio (OR) and 95% confidence intervals (95% CI) were adjusted for age, sex, education, smoking, physical, social and productive activity, multi-morbidity, metabolic syndrome and MMSE. Per standard deviation increase in TUG, POMA, GS and KES were significantly associated with incident MCI-dementia: TUG (OR = 2.84, 95% CI = 2.02-3.99), GS (OR = 2.17, 95% CI = 1.62-2.91), POMA (OR = 1.88, 95% CI = 1.22-2.92) and KES (OR = 1.52, 95% CI = 1.15-2.02). Adjusted OR remained significant only for TUG (OR = 1.52, 95% CI = 1.01-2.31) and GS (OR = 1.53, 95% CI = 1.08-2.16). Areas under the curve (AUC) for TUG (AUC = 0.729, 95% CI = 0.671-0.787) were significantly greater than GS (AUC = 0.683, 95% CI = 0.619-0.746), KES (AUC = 0.624, 95% CI = 0.558-0.689) and POMA (AUC = 0.561, 95% CI = 0.485-0.637). Similar associations with cognitive decline were significant though less pronounced, and adjusted ORs remained significant for TUG, GS and POMA. Functional mobility decline precedes incident MCI and early dementia. The TUG appears to be especially accurate in predicting the future risks of adverse cognitive outcomes. ClinicalTrials.gov NCT03405675. Registered 23 January 2018 (retrospectively registered).

Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment

AbstractBackgroundThe combinatorial effect of multiple genetic factors calculated as a polygenic risk score (PRS) has been studied to predict Alzheimer’s disease (AD) risk and evidence suggests that the predictability of PRS can be affected by the presence of APOE e4 allele substantially. Therefore, we aimed to evaluate the predictability of PRS on disease progression to AD depending on APOE ε4 carrier status and its interaction with APOE ε4 in mild cognitive impairment (MCI).MethodWe analyzed 732 MCI patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort with those who progressed to AD within 5 years post‐baseline (n=270) and remained stable as MCI (n=462). The predictability of PRSs including and excluding the APOE region (PRS+APOE and PRS‐APOE) on the conversion to AD and its interaction with APOE ε4 carrier status were assessed using Cox regression analyses. Gene set enrichment analysis of single nucleotide polymorphisms (SNPs) selected for PRS calculation was performed.ResultPRS+APOE (hazard ratio (HR) 1.468, 95% CI 1.335–1.615) and PRS‐APOE (HR 1.293, 95% CI 1.157–1.445) both were associated with a significantly increased risk of progression to dementia in MCI (Table 1). The interaction between PRS+APOE and APOE ε4 carrier status was significant with a p‐value of 3.78×10‐2 (Table 2). The association of PRSs with progression risk was stronger in APOE ε4 non‐carriers (PRS+APOE: HR 1.710, 95% CI 1.244–2.351, PRS‐APOE: HR 1.429, 95% CI 1.182–1.728) than APOE ε4 carriers in MCI (PRS+APOE: HR 1.167, 95% CI 1.005–1.355, PRS‐APOE: HR 1.172, 95% CI 1.020–1.346) (Table 1 and Figure 1). Gene set enrichment analysis identified 27 significant pathways including those linked to amyloid, lipid, and protein metabolisms (Figure 2).ConclusionThe results demonstrated that PRSs showed a significant interaction with APOE ε4 carrier status and PRSs including and excluding APOE regions could predict conversion of MCI to dementia with a stronger association in APOE ε4 non‐carriers than APOE ε4 carriers. This indicates PRS as a potential genetic predictor particularly for progression of MCI patients with no APOE ε4 alleles.

White matter hyperintensities and mild behavioural impairment: Findings from the MEMENTO Study

AbstractBackgroundMild behavioural impairment (MBI) is a neurobehavioural syndrome characterized by the onset and persistence of neuropsychiatric symptoms (NPS) in later life. While the ATN framework provides a robust overview of Alzheimer’s pathology, it does not fully capture the impact of small‐vessel cerebrovascular disease in the pathogenesis of dementia. White matter hyperintensities (WMH) may independently contribute to the development of Alzheimer’s dementia and predict risk of incident dementia in mild cognitive impairment (MCI). Few studies have established the link between NPS and WMH in MCI populations.MethodWe included 760 participants from the French MEMENTO study with MCI and WMH data. WMH volumetry on T2‐weighted fluid attenuated inversion recovery images was identified using WHASA software, visually verified with the Fazekas and Schmidt scale, and expressed in cm3. Mean age was 72.7 (SD 8.0) and 57.9% of participants were female. Neuropsychiatric Inventory items were transformed to MBI domains using a published algorithm. MBI status was based on symptom persistence: NPS at both baseline and 6‐months was considered MBI+ (n = 227), whereas non‐persistent NPS (i.e., NPS at either time point but not both) or no NPS at either baseline or 6‐months was considered MBI‐ (n=549). We investigated the association between MBI status and the outcome variable, WMH, using a linear regression model adjusted for age, sex, education, Mini‐Mental Status Exam (MMSE) score, and total intracranial volume.ResultMBI was present in 29.9% of participants (n = 227). MBI+ (i.e., persistent NPS) was significantly associated with lower MMSE score (p < 0.001) and male sex (p = 0.025). Compared to MBI‐, MBI+ was associated with 9.9% higher WMH volume [p = 0.006 (95% CI 2.8% to 18%), Table 1].ConclusionIn a memory clinic sample of older adults with MCI, MBI+, operationalized as persistent NPS, is associated with higher WMH. These findings extend the evidence base linking MBI with known dementia biomarkers and raise the possibility that some forms of MBI can be caused by vascular brain injury.

Physical exercise as a non-pharmacological strategy for reducing behavioral and psychological symptoms in elderly with mild cognitive impairment and dementia: a systematic review of randomized clinical trials.

Elderly people with dementia may exhibit behavioral and psychological symptoms throughout the course of disease. Non-pharmacological therapies, such as regular physical activity, are considered strategies for managing these symptoms. The aim of this study was to investigate whether participation in physical exercise programs is effective in reducing behavioral and neuropsychiatric symptoms in elderly people with Mild Cognitive Impairment (MCI) and dementia. A literature review was carried out in MEDLINE (PubMed), SciELO, Web of Science, Scopus and SPORTDiscus databases from 2010 to 2020. The eligible studies were randomized clinical trials involving elderly people with mild cognitive impairment or dementia and assessing changes in neuropsychiatric and psychological symptoms as primary or secondary outcomes. The studies had a group with only physical exercise as an intervention compared to a control group. Of 175 publications identified in the initial survey, only 7 studies met the eligibility criteria. Four out of 7 studies demonstrated positive effects in reducing behavioral symptoms, while the others did not report differences between gains according to the type of protocol. Moderate to intense aerobic and muscle strengthening exercises may have a potential benefit in the management of behavioral and psychological symptoms in dementia, but studies varied in their conclusions. This review indicates the need for further intervention studies to investigate, as a primary outcome, the absolute effect of physical exercise and its impact on behavioral and psychological symptoms in elderly people with MCI dementia, especially in the early stages of the disease.

Written Discourse Task Helps to Identify Progression from Mild Cognitive Impairment to Dementia

Purpose: We aimed to investigate: (1) the clinical, diagnostic value of a written discourse task, and (2) the relationship between executive functions and written discourse within the spectrum of individuals with mild cognitive impairment (MCI). Method: To determine whether written discourse performance predicts clinical course among individuals with MCI, we retrospectively classified individuals with MCI as converters (N = 26) who were later diagnosed with dementia or as a stable MCI group (N = 45). We quantified core word measures from written discourse samples obtained from the Cookie Theft picture description task. Result: Written discourse measures differentiated converters from the stable MCI group. Converters produced a fewer number of core words than the stable MCI group. A measure of executive function significantly predicted performance on the production of core words in written discourse for the converters. In a multivariable regression, production of core words remained the only explanatory variable closely associated with the progression to dementia in MCI. Conclusion: Written discourse tasks can predict the likelihood of MCI progressing to dementia, independently of recall and an executive function measure. Correlational results suggest that written discourse performance was associated with executive function as measured by the Trail Making Test. Our findings emphasize the usefulness of including written discourse tasks in language assessment batteries targeting preclinical dementia populations.

Slowing on quantitative EEG is associated with transition to dementia in mild cognitive impairment.

Electroencephalographic (EEG) abnormalities are greater in mild cognitive impairment (MCI) with Lewy bodies (MCI-LB) than in MCI due to Alzheimer's disease (MCI-AD) and may anticipate the onset of dementia. We aimed to assess whether quantitative EEG (qEEG) slowing would predict a higher annual hazard of dementia in MCI across these etiologies. MCI patients (n = 92) and healthy comparators (n = 31) provided qEEG recording and underwent longitudinal clinical and cognitive follow-up. Associations between qEEG slowing, measured by increased theta/alpha ratio, and clinical progression from MCI to dementia were estimated with a multistate transition model to account for death as a competing risk, while controlling for age, cognitive function, and etiology classified by an expert consensus panel.Over a mean follow-up of 1.5 years (SD = 0.5), 14 cases of incident dementia and 5 deaths were observed. Increased theta/alpha ratio on qEEG was associated with increased annual hazard of dementia (hazard ratio = 1.84, 95% CI: 1.01-3.35). This extends previous findings that MCI-LB features early functional changes, showing that qEEG slowing may anticipate the onset of dementia in prospectively identified MCI.

Depression and Conversion to Dementia in Mild Cognitive Impairment

Mild cognitive impairment (MCI) is a stage of aging that occurs between normal aging and dementia (precedes dementia). Patients with MCI have memory loss who is otherwise functioning normally and does not match the clinical diagnosis criteria for dementia. MCI is frequently accompanied by cognitive deficits and non-cognitive. One of the most frequent non-cognitive deficiencies is depression. Depression and mild cognitive impairment are closely associate particularly in the elderly and can progress into neurodegenerative disorders like dementia. This indicates that there is a connection that needs to be explored further. Through this review article, a theoretical review of the relationship between MCI with depression and its conversion to dementia.

Spotlight on the June 1 Issue

#### Notable in Neurology This Week This issue features an article that investigates how heterogeneity in disease progression influences the detection of treatment effects in Alzheimer disease trials; another determines the association between electroencephalographic seizure and unfavorable neurobehavioral outcomes in critically ill children. A featured Views & Reviews examines the effectiveness of vagus nerve stimulation in treating pediatric drug-resistant epilepsy. ### Progression to Dementia in Mild Cognitive Impairment With Lewy Bodies or Alzheimer Disease The rate of, and factors associated with, …

Neuropsychiatric profiles and conversion to dementia in mild cognitive impairment, a latent class analysis

Neuropsychiatric symptoms (NPS) have been recently addressed as risk factors of conversion to Alzheimer’s disease (AD) and other dementia types in patients diagnosed with Mild Cognitive Impairment (MCI). Our aim was to determine profiles based on the prominent NPS in MCI patients and to explore the predictive value of these profiles on conversion to specific types of dementia. A total of 2137 MCI patients monitored in a memory clinic were included in the study. Four NPS profiles emerged (classes), which were defined by preeminent symptoms: Irritability, Apathy, Anxiety/Depression and Asymptomatic. Irritability and Apathy were predictors of conversion to dementia (HR = 1.43 and 1.56, respectively). Anxiety/depression class showed no risk effect of conversion when compared to Asymptomatic class. Irritability class appeared as the most discriminant neuropsychiatric condition to identify non-AD converters (i.e., frontotemporal dementia, vascular dementia, Parkinson’s disease and dementia with Lewy Bodies). The findings revealed that consistent subgroups of MCI patients could be identified among comorbid basal NPS. The preeminent NPS showed to behave differentially on conversion to dementia, beyond AD. Therefore, NPS should be used as early diagnosis facilitators, and should also guide clinicians to detect patients with different illness trajectories in the progression of MCI.

Individualized prognosis of cognitive decline and dementia in mild cognitive impairment based on plasma biomarker combinations.

We developed models for individualized risk prediction of cognitive decline in mild cognitive impairment (MCI) using plasma biomarkers of β-amyloid (Aβ), tau and neurodegeneration. A total of 573 patients with MCI from the Swedish BioFINDER study and the Alzheimer's Disease Neuroimaging Initiative (ADNI) were included in the study. The primary outcomes were longitudinal cognition and conversion to Alzheimer's disease (AD) dementia. A model combining tau phosphorylated at threonine 181 (P-tau181) and neurofilament light (NfL), but not Aβ42/Aβ40, had the best prognosis performance of all models (area under the curve = 0.88 for 4-year conversion to AD in BioFINDER, validated in ADNI), was stronger than a basic model of age, sex, education and baseline cognition, and performed similarly to cerebrospinal fluid biomarkers. A publicly available online tool for individualized prognosis in MCI based on our combined plasma biomarker models is introduced. Combination of plasma biomarkers may be of high value to identify individuals with MCI who will progress to AD dementia in clinical trials and in clinical practice.

Later-Onset Hypertension Is Associated With Higher Risk of Dementia in Mild Cognitive Impairment.

To investigate the correlation between hypertension development and the progression of mild cognitive impairment (MCI) to dementia in middle-aged and elderly people. A population-based longitudinal cognition survey of people aged 55+ was conducted. The hypertension onset age was estimated by self-reported information and medical insurance card records. To study the effect of later-onset hypertension on dementia, the incidence of dementia was compared between the two groups. Of 277 hypertensive MCI participants without dementia, 56 (20.22%) progressed to dementia (MCIp) over the 6-year follow-up. The proportion of MCIp participants in the old-age-onset hypertension group (≥65 years) was higher than that in the middle-age-onset hypertension group (27.0 vs. 15.4%, respectively; X2 = 5.538, P = 0.019). In the old-age-onset hypertension group, the proportion of MCIp without diabetes mellitus was higher than those with diabetes mellitus (24.7 vs. 12.6%, respectively; X2 = 5.321, P = 0.021) and those with increased pulse pressure was higher than those without increased pulse pressure (33.3 vs. 15.4%, respectively; X2 = 3.902, P = 0.048). However, the cox proportional hazard showed that older age was the only risk factor for MCIp (HR = 0.618, p = 0.000). These results suggest that individuals with later-onset hypertension may have greater cognition decline, even with blood pressure maintained at 130/80 mmHg with antihypertensive management.

MMSE Subscale Scores as Useful Predictors of AD Conversion in Mild Cognitive Impairment.

PurposeThis study was performed to examine the usefulness of subscores on the Mini-Mental State Examination (MMSE) for predicting the progression of Alzheimer’s disease (AD) dementia in individuals with mild cognitive impairment (MCI).Patients and MethodsA total of 306 MCI individuals in the Alzheimer’s Disease Neuroimaging Initiative database were included in the study. Standardized clinical and neuropsychological tests were performed at baseline and at 2-year follow-up. Logistic regression analysis was conducted to examine the MMSE total and subscale scores to predict progression to AD dementia in MCI individuals.ResultsThe MMSE total score and the MMSE memory, orientation, and construction subscores were inversely associated with AD progression after controlling for all potential confounders; MMSE attention and language subscores were not correlated with AD progression. The MMSE delayed recall score among the MMSE memory subscores and the MMSE time score among the orientation subscores, especially week and day, were inversely associated with AD progression; the MMSE immediate recall and place scores were not correlated with progression.ConclusionOur findings suggest that the MMSE memory, orientation, and construction subscores, which are simple and readily available clinical measures, could provide useful information to predict AD dementia progression in MCI individuals in practical clinical settings.

Which factors can we control the transition from mild cognitive impairment to dementia?

Mild cognitive impairment (MCI) is a clinical condition in the transitional stage between healthy aging and dementia. In this study, we investigated the risk factors and the development of dementia in MCI patients.Seventy six patients who diagnosed MCI, according to the Petersen criteria, over sixty-years old, and risk factors in transition to dementia were investigated. Neurological examinations, laboratory tests, systemic comorbidities, mini-mental state examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale of the patients every 3–6 months were investigated. Dementia developed in 44.7% of MCI patients. Vascular risk factors were the most prominent risk factors in the transition from MCI to dementia (p = 0.000).Increased vascular risk factors and advancing age in MCI patients accelerate the transition to dementia. Therefore, modifiable vascular risk factors, which are significant factors in the transition to dementia, should be controlled and these patients should be closely monitored.

Social Cognition in Rehabilitation Context: Different Evolution of Affective and Cognitive Theory of Mind in Mild Cognitive Impairment.

Maintaining social skills such as Theory of Mind (ToM) competences is important to counteract the conversion into dementia in Mild Cognitive Impairment (MCI). Multidimensional nonpharmacological interventions demonstrated their potential in improving cognitive and behavioral abilities; however, little is known about the long-term effect of such interventions on social skills in people with MCI. The aim of this longitudinal study was to monitor ToM competences considering both cognitive and affective domains in an amnestic MCI (aMCI) sample involved in a home-based multistimulation treatment (MST@H). 30 aMCI subjects (M : F = 15 : 15; mean age ± SD = 77.00 ± 4.60) were enrolled, and three steps of evaluation with neuropsychological tests and ToM tasks have been implemented. 21 healthy controls (HC) were also included (M : F = 9 : 12; mean age ± SD = 74.95 ± 3.88) to characterize the aMCI sample regarding differences in ToM performance compared to HC at the baseline evaluation. Our results show that the aMCI group statistically significantly underperformed the HC group only in the advanced ToM tasks, confirming an initial decline of high-level ToM competences in this population. The longitudinal evaluation revealed time changes not only in some subcognitive domains of MoCA (memory and executive functions) but also in cognitive and affective ToM dimensions in aMCI subjects. Our findings suggest that cognitive and affective ToM can be considered useful outcome measures to test the long-term effect of treatment over time.

A Comprehensive Visual Rating Scale for Predicting Progression from Mild Cognitive Impairment to Dementia in Patients with Alzheimer's Pathology or Suspected Non-Alzheimer's Pathology.

Background and PurposeTo identify biomarkers for prediction of the progression to dementia in mild cognitive impairment (MCI) patients, evaluation of brain structure changes has been validated by a comprehensive visual grading scale (CVRS) through magnetic resonance imaging (MRI). In this study, we specifically elucidated for the cognitive change of MCI patients classified based on AT(N) pathological status classification during the follow-up period of 3 years through the CVRS.MethodsThe 301 patients with initial MCI visited at least once for follow-up period. The data used in this study were obtained from the Alzheimer's disease (AD) Neuroimaging Initiative study. Brain atrophy was assessed by CVRS using MRI. AT(N) profiles were classified by cerebrospinal fluid abnormality. Based on the AT(N) assessment, all individuals in this study were divided into 3 groups (normal state biomarker, suspected non-Alzheimer's pathology [SNAP], or Alzheimer's continuum). The cox regression was used to analyze the hazard ratios of CVRS for progression to dementia.ResultsSixty-three progressed and 238 remained stable to dementia and the CVRS (mean±standard deviation) had significant difference between progressive MCI and stable MCI (p<0.001). Univariate and multivariate cox regression results (p<0.001) showed the independence of initial CVRS as a predictor for the progression to dementia. Moreover, comparing the classified AT(N) pathology group, SNAP and AD, effectiveness of CVRS as a predictor was verified only in Alzheimer's continuum.ConclusionsThe initial CVRS score as a predictor of dementia progression was independently validated at the stage of Alzheimer's progression among AT(N) pathologically differentiated MCI.

Polypharmacy and gait speed in individuals with mild cognitive impairment.

Polypharmacy has been reported to be associated with poor outcomes, including falls and frailty, in older populations. Past studies have found that slower walking speed is a good predictor of progression to frank dementia in mild cognitive impairment (MCI). Some studies of the general population reported that polypharmacy was associated with slower gait speed; however, it remains to be elucidated whether polypharmacy affects gait speed even in individuals with MCI, who already have some deterioration in gait compared with cognitively preserved individuals. The current study explored the association between the number of medications and gait speed in older adults with MCI who have a Clinical Dementia Rating score of 0.5. A total of 128 individuals with MCI were included in the present study. The participants were divided into three groups according to the number of medications they were taking: up to four medications was non-polypharmacy; five to nine medications was polypharmacy; and ≥10 medications was hyperpolypharmacy. The background characteristics were compared by analysis of variance for numerical numbers, and by χ2 analysis for categorical factors. Multiple regression and logistic analysis were applied to investigate the association between gait speed and polypharmacy status or number of medications. Gait speed was significantly negatively associated with hyperpolypharmacy status and the number of medications. Slow gait speed (<1 m/s) was also significantly associated with polypharmacy status and the number of medications. We found that polypharmacy was associated with slow gait speed in older adults with MCI. Geriatr Gerontol Int 2019; 19: 730-735.